Lin Ruoxi, Li Haixiu, Xiao Yiren, Wang Zhuo, Liu Licheng, Saalbach Gerhard, Martins Carlo, Furry Matthew, Vanderwal Christopher D, Martin Cathie, Tatsis Evangelos C
CAS Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai 200032, China; John Innes Centre, Norwich NR4 7UH, UK.
CAS Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai 200032, China; School of Life Sciences, East China Normal University, Shanghai 200241, China.
Plant Commun. 2025 May 12;6(5):101286. doi: 10.1016/j.xplc.2025.101286. Epub 2025 Feb 18.
Salvia species native to the Americas are rich in valuable bioactive furanoclerodanes like the psychoactive salvinorin A found in Salvia divinorum, which is used in the treatment of opioid addiction. However, relatively little is known about their biosynthesis. To address this, we investigated the biosynthesis of salviarin, the most abundant furanoclerodane structure in the ornamental sage Salvia splendens. Using a self-organizing map and mutual rank analysis of RNA-seq co-expression data, we identified three cytochrome P450 enzymes responsible for the consecutive conversion of kolavenol into the salviarin precursors: annonene, hardwickiic acid, and hautriwaic acid. Annonene and hardwickiic acid have been proposed as intermediates in the biosynthesis of salvinorin A, and we therefore tested for a common evolutionary origin of the furanoclerodane pathway in these Salvia species by searching for homologous genes in available data for S. divinorum. The enzymes encoded by orthologous genes from S. divinorum displayed kolavenol synthase, annonene synthase, and hardwickiic acid synthase activity, respectively, supporting the view that these are intermediate steps in the biosynthesis of salvinorin A. We further investigated the origin of annonene synthase and the role of gene duplication in the evolution of this specific activity. Our work shows how S. splendens can serve as a model species for the study of furanoclerodane biosynthesis in Salvia species, contributes to understanding the evolution of specialized metabolism in plants, and provides new tools for the production of salvinorin A in biotechnological chassis.
原产于美洲的鼠尾草属植物富含珍贵的生物活性呋喃贝壳杉烷，比如在神圣鼠尾草中发现的具有精神活性的萨尔维诺灵A，它被用于治疗阿片类药物成瘾。然而，人们对它们的生物合成了解相对较少。为了解决这个问题，我们研究了观赏鼠尾草一串红中最丰富的呋喃贝壳杉烷结构萨尔维阿林的生物合成。通过对RNA测序共表达数据进行自组织映射和互秩分析，我们鉴定出三种细胞色素P450酶，它们负责将可乐韦醇连续转化为萨尔维阿林的前体：番荔枝烯、哈德威克酸和豪特里瓦酸。番荔枝烯和哈德威克酸已被认为是萨尔维诺灵A生物合成的中间体，因此我们通过在神圣鼠尾草的现有数据中搜索同源基因，来测试这些鼠尾草属植物中呋喃贝壳杉烷途径的共同进化起源。来自神圣鼠尾草的直系同源基因编码的酶分别表现出可乐韦醇合酶、番荔枝烯合酶和哈德威克酸合酶活性，这支持了这些是萨尔维诺灵A生物合成中间步骤的观点。我们进一步研究了番荔枝烯合酶的起源以及基因复制在这种特定活性进化中的作用。我们的工作展示了一串红如何能够作为研究鼠尾草属植物中呋喃贝壳杉烷生物合成的模式物种，有助于理解植物中特殊代谢的进化，并为在生物技术底盘中生产萨尔维诺灵A提供新工具。
